Cardiometabolic Risk Markers in Children With Obesity and Variants in MC4R Pathway-related Genes.

Context: Variants in melanocortin 4 receptor (MC4R) pathway-related genes have been associated with obesity. The association of these variants with cardiometabolic parameters are not fully known. Objective: We compared the severity of obesity and cardiometabolic risk markers in children with MC4R pathway-related clinically reported genetic variants relative to children without these variants. Methods: A retrospective chart review was performed in children with obesity who underwent multigene panel testing for monogenic obesity. Results: Data on a total of 104 children were examined, with 93 (89%) identified as White. Thirty-nine (37.5%) patients had clinically reported variants in the MC4R pathway, and the remaining 65 patients did not have reported MC4R pathway-related variants. Among the MC4R-related variants, PCSK1 risk alleles were most common, reported in 15 children (14%). The maximum body mass index percent of the 95th percentile was not different between groups (P = .116). Low-density lipoprotein cholesterol (LDL-C) was not different between groups (P = .132). However, subgroup analysis demonstrated higher LDL cholesterol in children with the PCSK1 c.661A>G risk allele relative to those with MC4R-related variant of uncertain significance (P = .047), negative genetic testing (P = .012), and those with non-MC4R related variants (P = .048). The blood pressure, fasting glucose, hemoglobin A1C, total cholesterol, alanine transaminase, and high-density lipoprotein cholesterol were not different between groups. Conclusion: Variants in the MC4R pathway-related genes were not associated with severity of obesity and cardiometabolic risk markers except for the c.661A>G PCSK1 risk allele, which was associated with higher LDL-C levels.

An infant developing hypercalcemia and hypophosphatemia due to the use of exclusively almond milk.

OBJECTIVES: Plant-based milk alternatives are increasingly utilized in children with cow milk allergy, lactose intolerance, and personal preference. However, notable differences exist in mineral content between cow milk and plant-based alternatives. Almond milk, in particular, varies in mineral and caloric content across different brands. This case report highlights a toddler who developed hypercalcemia and hypophosphatemia attributed to almond milk consumption. CASE PRESENTATION: A fourteen-month-old girl with a history of biliary atresia underwent liver transplant at seven months of age. She was exclusively consuming almond milk for two months prior to presentation. She was admitted to the hospital for severe hypercalcemia (14.6 mg/dL) and hypophosphatemia (1.6 mg/dL). She had elevated random urine calcium to creatinine ratio (2.56 mg/g) and low urine phosphorus to creatinine ratio (<0.44 mg/g) were noted. Parathyroid hormone (PTH) level was appropriately suppressed (<6 pg/mL), while 1,25 dihydroxyvitamin D level was slightly elevated at 88 pg/mL. Initial management included intravenous fluids, followed by a switch to a formula with higher phosphorus and lower calcium concentrations. The patient was discharged after six days with normalized calcium and phosphorus levels, which remained within the normal range. CONCLUSIONS: Although plant-derived milk serves as a viable alternative to cow milk, careful consideration of mineral content, particularly in infants and toddlers, is imperative. Sole reliance on almond milk for nutritional needs in this population is not recommended. Caregivers should be informed about the potential risks associated with almond milk consumption in infants and toddlers.

Glucagon fill rates and cost among children and adolescents with type 1 diabetes in the United States, 2011-2021.

AIMS: To characterize glucagon fill rates and costs among youth with type 1 diabetes mellitus (T1DM). METHODS: Claims-based analysis of commercially-insured youth with T1DM included in OptumLabs® Data Warehouse between 2011 and 2021. Glucagon fill rates and costs were calculated overall and by formulation (injectable, intranasal, autoinjector, and pre-filled syringe). Sociodemographic and clinical factors associated with glucagon fills were examined using Cox regression. RESULTS: We identified 13,267 children with T1DM (76.4% non-Hispanic White). Over mean follow-up of 2.81 years (SD 2.62), 70.0% filled glucagon, with stable fill rates from 2011 to 2021. Intranasal glucagon had rapid uptake following initial approval, and it accounted for almost half (46.6%) of all glucagon fills by 2021. Family income was positively associated with glucagon fills in a stepwise fashion (HR 1.39 [95% CI 1.27-1.52] for annual household income ≥$200,000 vs. <$40,000), while Black race was negatively associated with fills (HR 0.83 [95% CI 0.76-0.91]) compared to White race). Annual mean out-of-pocket costs ranged from $21-$68 (IQR $29-$44). CONCLUSION: Roughly 30% of commercially-insured youth with T1DM may lack access to unexpired glucagon, with significant disparities among Black and low-income patients. Health systems, clinicians, schools, and caregivers should work together to ensure children have reliable access to this critical medication.

Copeptin levels in hospitalized infants and children with suspected vasopressin-dependent disorders: a case series.

OBJECTIVES: There have been recent advances assessing copeptin levels in adults with suspected disorders of vasopressin release. Very limited data exits on copeptin levels in children and infants, especially in a critically-ill hospitalized population where hyper- and hypo-natremia are very common. Our objective is to describe the institutional experience assessing copeptin levels in hospitalized infants and children with hyper- or hypo-natremia. METHODS: We performed a single-center retrospective case series of all infants, children, and adolescents who had an ultrasensitive plasma copeptin level obtained between 2019-2021. RESULTS: A total of 29 critically ill patients (6 infants) were identified with 38 % of patients having copeptin levels after neurosurgical procedures for tumors or trauma. Approximately 13/17 children with hypernatremia had central diabetes insipidus (central diabetes insipidus) to diagnose CDI, A copeptin level ≤ 4.9 pmol/L resulted in an 88 % sensitivity (95 % CI 47-99 %), and 66 % specificity (95 % CI 30-93 %). Amongst those with hyponatremia levels were more variable, 8/12 children had syndrome of inappropriate antidiuresis (SIAD) with copeptin levels ranging 4.7-72.6 pmol/L. CONCLUSIONS: While difficult to conclude due to multiple limitations, this case series highlights that typical copeptin cutoffs used to diagnose DI in adults in an ambulatory setting may also translate to a critically-ill pediatric population. Large prospective studies are needed to confirm this observation. In addition, postoperative copeptin levels could potentially be utilized as an additional marker to predict permanent from transient DI, but much larger studies are needed. Further work is needed to establish normative copeptin levels in infants and patients with SIAD.

Adolescents with Type 2 Diabetes: Overcoming Barriers to Effective Weight Management.

The prevalence of type 2 diabetes (T2DM) among children and adolescents has remarkably increased in the last two decades, particularly among ethnic minorities. Management of T2DM is challenging in the adolescent population due to a constellation of factors, including biological, socioeconomic, cultural, and psychological barriers. Weight reduction is an essential component in management of T2DM as weight loss is associated with improvement in insulin sensitivity and glycemic status. A family centered and culturally appropriate approach offered by a multidisciplinary team is crucial to address the biological, psychosocial, cultural, and financial barriers to weight management in youth with T2DM. Lifestyle interventions and pharmacotherapy have shown modest efficacy in achieving weight reduction in adolescents with T2DM. Bariatric surgery is associated with excellent weight reduction and remission of T2DM in youth. Emerging therapies for weight reduction in youth include digital technologies, newer GLP-1 agonists and endoscopic procedures.

Bilateral Femoral Fracture in an Adolescent Male Due to Severe Vitamin D Deficiency.

PURPOSE/BACKGROUND: Mild to moderate vitamin D deficiency is common in pediatric patients in the U.S. Severe hypovitaminosis D has been linked to specific risk factors, such as female gender, obesity, winter season, darker skin, lack of exposure to the sun, and low vitamin D intake. It has been reported that adolescents usually experience less severe clinical symptoms than young children with vitamin D deficiency. We present a previously healthy 15-year-old Caucasian male with bilateral spontaneous femoral fracture due to severe hypovitaminosis rickets. He had unusual eating habits such as avoiding dairy, vegetables, and fruits. In addition to always preferring to eat alone due to anxiety. Patient is underweight with a BMI z score of -4.05 at time of presentation. Due to lack of interest in physical activities, the patient spent most of his time indoors. DESIGN/METHODS: This is a case report of a patient who presented to the children's hospital for further workup for bilateral spontaneous femoral fractures. FINDINGS/RESULTS: Laboratory work up revealed that his 25 hydoxy-vitamin D level was less than 4 ng/ml, calcium level was 5.7 mg/dl (8.4-10.5mg/dL), and phosphorus was 3.5 mg/dl (3.7-4.7 mg/dl). His intact parathyroid hormone was elevated at 555 pg/ml (14-95 pg/ml) and alkaline phosphatase was elevated at 777 U/L (91-339 U/L). A wrist x-ray showed widening of the distal radial and ulnar metaphyses with metaphyseal cupping. Further labs showed macrocytic anemia and severe vitamin B12 deficiency. Workup for malabsorption was negative. Patient underwent bilateral open hip reduction internal fixation. Hypovitaminosis D and hypocalcemia were treated with calcium carbonate and oral vitamin D3 supplements. His follow up laboratory evaluation showed normalization of his calcium, phosphorus, PTH, alkaline phosphatase, and vitamin D levels. Repeat wrist X-ray two months later revealed marked improvement in the appearance of the distal radial and ulnar growth plates and metaphyseal regions. CONCLUSIONS: This patient's vitamin D deficiency/rickets was found to be secondary to malnutrition due to limited intake, along with limited sunlight exposure. We recommend that a detailed dietary history is obtained in every adolescent patient to evaluate for proper vitamin D intake, especially in patients who are significantly underweight. If vitamin D deficiency is expected, vitamin D level should be checked and appropriate treatment should be initiated once vitamin D insufficiency is confirmed.

Efficacy of Pharmacological Therapies for the Prevention of Fractures in Postmenopausal Women: A Network Meta-Analysis.

BACKGROUND: Osteoporosis and osteopenia are associated with increased fracture incidence in postmenopausal women. We aimed to determine the comparative effectiveness of various available pharmacological therapies. METHODS: We searched MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, ISI Web of Science, and Scopus for randomized controlled trials that enrolled postmenopausal women with primary osteoporosis and evaluated the risk of hip, vertebral, or nonvertebral fractures. A network meta-analysis was conducted using the multivariate random effects method. RESULTS: We included 107 trials (193,987 postmenopausal women; mean age, 66 years; 55% white; median follow-up, 28 months). A significant reduction in hip fractures was observed with romosozumab, alendronate, zoledronate, risedronate, denosumab, estrogen with progesterone, and calcium in combination with vitamin D. A significant reduction in nonvertebral fractures was observed with abaloparatide, romosozumab, denosumab, teriparatide, alendronate, risedronate, zoledronate, lasofoxifene, tibolone, estrogen with progesterone, and vitamin D. A significant reduction in vertebral fractures was observed with abaloparatide, teriparatide, parathyroid hormone 1-84, romosozumab, strontium ranelate, denosumab, zoledronate, risedronate, alendronate, ibandronate, raloxifene, bazedoxifene, lasofoxifene, estrogen with progesterone, tibolone, and calcitonin. Teriparatide, abaloparatide, denosumab, and romosozumab were associated with the highest relative risk reductions, whereas ibandronate and selective estrogen receptor modulators had lower efficacy. The evidence for the treatment of fractures with vitamin D and calcium remains limited despite numerous large trials. CONCLUSIONS: This network meta-analysis provides comparative effective estimates for the various available treatments to reduce the risk of fragility fractures in postmenopausal women.

Diagnostic accuracy of the McGill thyroid nodule score in paediatric patients.

INTRODUCTION: Thyroid cancer is the most common paediatric endocrine cancer; accurate diagnosis and prompt management of paediatric thyroid nodules is critical. The McGill Thyroid Nodule Score (MTNS), based upon clinical, ultrasound (US) and cytology criteria, has recently been modified and studied in a pilot paediatric group with good results. We aim to describe the diagnostic accuracy of the paediatric modified MTNS (PMTNS) in a large paediatric cohort. METHODS: We utilized an established retrospective cohort between 1996 and 2015 of 99 patients ≤21 years old with 131 thyroid nodules. Two experienced paediatric radiologists, blinded to pathology and radiology reports, reviewed US features. We abstracted cytology, histology and laboratory results, assigning each nodule a PMTNS. PMTNS performance was compared to FNA and histology. RESULTS: Approximately 33% of nodules were malignant. The cohort was predominantly adolescent (mean age 15.4 ± 3.8 years). The average PMTNS for malignant and benign nodules, based on final histology, was 12.7 ± 4.3 and 1.7 ± 2.9, respectively. A PMTNS ≥8 resulted in a 93.2% sensitivity and 93.1% specificity for detecting malignancy, while a PMTNS ≥9 resulted in a 90.9% sensitivity and 96.6% specificity. However, Bethesda cytology category ≥4 independently had a 97.7% sensitivity and 94.0% specificity for detecting malignancy. The PMTNS had diminishing diagnostic accuracy in younger children compared with older children. CONCLUSION: Paediatric modified McGill Thyroid Nodule Score predicts malignancy, perhaps due to the score's emphasis on cytology results; however, the score is less accurate in younger patients. While cytology results remain reliable, further work is needed to develop a non-invasive scoring system to predict malignancy in children.

Ultrasonography and the American Thyroid Association Ultrasound-Based Risk Stratification Tool: Utility in Pediatric and Adolescent Thyroid Nodules.

BACKGROUND: Pediatric thyroid nodules are more likely to be malignant compared to those in adults and may have different concerning ultrasound (US) features. Recent adult guidelines stratify malignancy risk by US features. Our aim is to (1) describe and confirm US features that predict pediatric malignancy, and (2) apply the Adult American Thyroid Association (ATA) Risk Stratification Guidelines to a large pediatric cohort. METHODS: We identified 112 children with 145 thyroid nodules from 1996 to 2015. Two blinded pediatric radiologists independently read all US images, described multiple features, and reported their overall impression: benign, indeterminate, or malignant. Each nodule was assigned an ATA risk stratification category. Radiologists' impressions and ATA risk stratification were compared to histology and cytology results. RESULTS: Multiple US features including a solid composition, presence of microcalcifications, irregular margins, increased blood flow, and hypoechogenicity were associated with increased odds of malignancy. ATA risk stratification correlated with the radiologists' overall impression (p < 0.001). The sensitivity for detecting malignancy was comparable between both ATA stratification (91%) and the radiologists' overall impression (90%). The specificity of the radiologists' malignant overall impression (80%) was better compared to the ATA high risk stratification (54%). CONCLUSIONS: At our institution, pediatric radiologists' overall impressions had similar sensitivity but better specificity for detecting malignancy than the ATA risk stratification tool by our convention. However, neither US-based methods perfectly discriminated benign from malignant nodules, supporting the continued need for fine needle aspiration for suspicious nodules. Further work is needed to develop an US-based scoring system specific to pediatric patients.

Transient Neonatal Diabetes due to a Mutation in KCNJ11 in a Child with Klinefelter Syndrome.

Klinefelter syndrome is the most frequent chromosomal aneuploidy in males occurring in about 1 in 660 males. Epidemiological studies have demonstrated increased risk of type 1 diabetes and type 2 diabetes in adults with Klinefelter syndrome. There is only one previous report of neonatal diabetes in a patient with Klinefelter syndrome. We report transient neonatal diabetes due to a pathogenic heterozygous variant in KCNJ11 in a male infant with Klinefelter syndrome. A 78-day old male infant was noted to have sustained hyperglycemia with serum glucose ranging between 148 mg/dL (8.2 mmol/L) and 381 mg/dL (21.2 mmol/L) three days after undergoing a complete repair of an atrioventricular defect. Hemoglobin A1c was 6.6%. The patient was born at term with a birth weight of 2.16 kg following a pregnancy complicated by gestational diabetes that was controlled with diet. The patient was initially started on a continuous intravenous insulin drip and subsequently placed on subcutaneous insulin (glargine, human isophane and regular insulin). Insulin was gradually decreased and eventually discontinued at seven months of age. Chromosomal microarray at 11 weeks of age showed XXY and a panel-based, molecular test for neonatal diabetes revealed a pathogenic heterozygous variant c.685G>A (p.Glu229Lys) in KCNJ11. The patient is now 34 months old and continues to have normal fasting and post-prandial glucose and HbA1C levels. The patient will need prospective follow up for assessment of his glycemic status. To our knowledge this is the second reported case of neonatal diabetes in an infant with Klinefelter syndrome and the first due to a mutation in the KCNJ11 in a patient with Klinefelter syndrome.

Treatments to Prevent Bone Loss in Functional Hypothalamic Amenorrhea: A Systematic Review and Meta-Analysis.

OBJECTIVE: We conducted a systematic review and meta-analysis of studies that evaluated the effect of hormonal therapy [estrogen therapy including oral contraceptive pills (OCP)] and bisphosphonates in preventing bone loss in patients with functional hypothalamic amenorrhea (FHA). METHODS: We searched several electronic databases for controlled and noncontrolled studies that enrolled females of any age presenting with FHA (including athletic, weight loss, and stress-associated amenorrhea/oligomenorrhea) through 9 January 2017. The outcomes of interest were fractures and bone mineral density (BMD). Random effects meta-analysis was used to pool outcomes across studies expressed as weighted mean difference and 95% confidence interval (CI). RESULTS: Nine studies reporting on 280 patients that received different hormonal therapies were included. We did not identify studies that evaluated bisphosphonates. Meta-analysis demonstrated a statistically significant increase in BMD of the lumbar spine in patients receiving hormonal therapy after a median follow-up of 12 months (weighted mean difference, 0.032 g/cm2; 95% CI, 0.017 to 0.047; percentage change in BMD, 3.30%; 95% CI, 1.74 to 4.86). There was no substantial effect of receiving hormonal therapy on BMD of the femoral neck, trochanteric region, Ward triangle, or total body BMD. The quality of evidence was low because of the high risk of bias, imprecision (small sample size), and indirectness (as BMD is a surrogate outcome). None of the studies reported the incidence of fractures. CONCLUSION: The current evidence does not support using hormonal therapy for the sole purpose of improving bone health in patients with FHA. There are no data about bisphosphonates in this population.

Can the source of hyperandrogenism in adolescents with polycystic ovary syndrome predict metabolic phenotype?

In this study, we demonstrated an association between adrenal hyperandrogenism, as determined by dehydroepiandrostenedione-to-free testosterone (DHEA-S/FT) ratio, and metabolic phenotype in obese and lean adolescents with polycystic ovary syndrome (PCOS). We compared 64 overweight/obese adolescents with PCOS (PCOS-O) with 18 lean (PCOS-L) adolescents. We analyzed the association between DHEA-S/FT ratios and metabolic parameters. Patients in the PCOS-O group were younger (median [interquartile range]) than those in the PCOS-L group (15 [15-17] vs. 16 [16-17] years; p = .04). The median DHEA-S/FT ratio and total testosterone concentrations did not differ. However, androstenedione concentrations were higher in the PCOS-L group (p = .02) and free testosterone levels lower in the PCOS-L group compared with the PCOS-O group (p = .02). Insulin resistance was present in 30 of 64 (46.9%) adolescents with PCOS-O compared with 1 of 18 (5.6%) with PCOS-L (p = .001). A significant negative correlation between DHEA-S/FT ratios and insulin concentrations in PCOS-O (p = .03) and PCOS-L (p = .04) groups was noted. In the PCOS-O group, the DHEA-S/FT ratio was negatively associated with serum triglyceride (p = .03) and total cholesterol concentrations (p = .02). We conclude that in adolescents with PCOS, a higher ratio of adrenal to ovarian androgens, signified by DHEA-S/FT, may be associated with a more favorable metabolic phenotype.

The Association of Weight Loss and Cardiometabolic Outcomes in Obese Children: Systematic Review and Meta-regression.

Background: Excess body weight in children is associated with multiple immediate and long-term medical comorbidities. We aimed to identify the degree of reduction in excess body weight associated with cardiometabolic changes (lipid panel, liver function tests, systolic blood pressure (SBP), diastolic blood pressure, glycosylated hemoglobin, and fasting blood glucose) in overweight and obese children. Methods: We conducted a comprehensive search of MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, and Scopus through February 12, 2015. We included randomized controlled trials and cohort studies that evaluated interventions to treat pediatric obesity (medication, surgery, lifestyle, and community-based interventions) with ≥ a 6-month follow-up. We used a random effects meta-regression approach to assess the association between body mass index (BMI)/weight and cardiometabolic changes. Results: We included 42 studies (37 randomized controlled trials and five cohorts) enrolling 3807 children (mean age, 12.2 years; weight, 74.7 kg; and BMI, 31.7 kg/m2). Studies had overall moderate to low risk of bias. A 1-mm Hg decrease in SBP was significantly associated with a decrease of 0.16 kg/m2 (P = .04) in BMI. A 1-mg/dL increase in HDL was significantly associated with a 0.74-kg decrease in weight (P = .02). A 1-mg/dL decrease in triglycerides was significantly associated with a 0.1-kg decrease in weight (P = .03). The remaining associations were not statistically significant. Conclusions: Weight reduction in children is associated with significant changes in several cardiometabolic outcomes, particularly HDL, SBP, and triglycerides. The magnitude of improvement may help in setting expectations and may inform shared decision-making and counseling.

ORAL VERSUS TRANSDERMAL ESTROGEN IN TURNER SYNDROME: A SYSTEMATIC REVIEW AND META-ANALYSIS.

OBJECTIVE: To conduct a systematic review and meta-analysis comparing transdermal estrogens (TDEs) versus oral estrogens (OEs) in Turner syndrome (TS). METHODS: Randomized trials and observational comparative studies with a minimal follow-up of 6 months for skeletal and metabolic outcomes and serum hormone changes were included. Outcomes were pooled with a random effects model and are reported as mean differences between OE and TDE groups and 95% confidence intervals (CIs). RESULTS: Of 845 candidate references, 4 studies were included. Both OEs and TDEs were associated with an increase in whole-body bone mineral density (BMD) z-score, with TDE therapy displaying a greater increase. OEs were associated with higher fasting glucose and total cholesterol. Both OEs and TDEs reduced low-density lipo-protein cholesterol (LDL-C) and increased high-density lipoprotein cholesterol (HDL-C), with OEs providing a more favorable effect. The use of 17-ß estradiol was associated with a higher total cholesterol and lower LDL-C than TDE. No statistically significant difference was found between OEs and TDEs in body mass index, fat mass, fat free mass, insulin-like growth factor 1, insulin-like growth factor binding protein 3, fasting insulin, triglycerides, estradiol, or estrone levels. CONCLUSION: In girls with TS, TDEs may be associated with a more beneficial effect on fasting glucose, cholesterol, and whole-body BMD. However, OEs have a more favorable impact on LDL-C and HDL-C. 17-ß estradiol has a more favorable effect on LDL-C. ABBREVIATIONS: BMI = body mass index BMD = bone mineral density CI = confidence interval HDL-C = high density lipo-protein-cholesterol IGF-1 = insulin-like growth factor 1 IGF-BP3 = insulin-like growth factor binding protein 3 LDL-C = low density lipoprotein-cholesterol MD = mean difference OE = oral estrogen RCT = randomized controlled trial TDE = transdermal estrogen TS = Turner syndrome.

GLUCOCORTICOID REPLACEMENT REGIMENS IN CHRONIC ADRENAL INSUFFICIENCY: A SYSTEMATIC REVIEW AND META-ANALYSIS.

OBJECTIVE: Various glucocorticoid (GC) regimens have been used in the treatment of patients with adrenal insufficiency, yet the differences between such regimens on health outcomes are unclear. We performed a systematic review and meta-analysis to compare the effects of GC regimens on quality of life (QoL), bone density, incidence of adrenal crisis, and death. In pediatric studies, we also searched for final adult height. METHODS: We searched 6 databases through July 2016. Studies were selected and appraised by independent reviewers. Data were pooled using the profile likelihood random-effects model. RESULTS: We included 34 studies. We found no difference in QoL scores between higher (≥30 mg/day of hydrocortisone [HC] equivalence) vs. lower daily doses (<30 mg/day of HC equivalence) (P = .15) or based on frequency of daily dosing (once, twice or thrice daily). Extended-release (1 study), dual-/modified-release (3 studies), and continuous subcutaneous (3 studies) forms of GCs were associated with higher QoL scores. There was no significant association between dose and type of GC and the incidence of adrenal crises. The effect on bone mineral density was heterogeneous. No data were available on mortality or final adult height in children. The quality of evidence was low due to increased risk of bias, imprecision, and heterogeneity. CONCLUSION: Extended-/dual-release, and continuous subcutaneous forms of GC may be associated with higher QoL scores. However, this is derived from short-term and imprecise evidence, warranting low confidence. ABBREVIATIONS: AI = adrenal insufficiency BMD = bone mineral density GC = glucocorticoids HC = hydrocortisone QoL = quality of life RCT = randomized controlled trial.

The Association of Weight Loss and Cardiometabolic Outcomes in Obese Children: Systematic Review and Meta-regression.

BACKGROUND: Excess body weight in children is associated with multiple immediate and long-term medical comorbidities. We aimed to identify the degree of reduction in excess body weight associated with cardiometabolic changes (lipid panel, liver function tests, systolic blood pressure (SBP), diastolic blood pressure, glycosylated hemoglobin, and fasting blood glucose) in overweight and obese children. METHODS: We conducted a comprehensive search of MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, and Scopus through February 12, 2015. We included randomized controlled trials and cohort studies that evaluated interventions to treat pediatric obesity (medication, surgery, lifestyle, and community-based interventions) with ≥ a 6-month follow-up. We used a random effects meta-regression approach to assess the association between body mass index (BMI)/weight and cardiometabolic changes. RESULTS: We included 42 studies (37 randomized controlled trials and five cohorts) enrolling 3807 children (mean age, 12.2 years; weight, 74.7 kg; and BMI, 31.7 kg/m2). Studies had overall moderate to low risk of bias. A 1-mm Hg decrease in SBP was significantly associated with a decrease of 0.16 kg/m2 (P = .04) in BMI. A 1-mg/dL increase in HDL was significantly associated with a 0.74-kg decrease in weight (P = .02). A 1-mg/dL decrease in triglycerides was significantly associated with a 0.1-kg decrease in weight (P = .03). The remaining associations were not statistically significant. CONCLUSIONS: Weight reduction in children is associated with significant changes in several cardiometabolic outcomes, particularly HDL, SBP, and triglycerides. The magnitude of improvement may help in setting expectations and may inform shared decision-making and counseling.

Diagnostic accuracy of ultrasound-guided fine needle aspiration biopsy for thyroid malignancy: systematic review and meta-analysis.

PURPOSE: To systematically appraise and summarize the available evidence about the diagnostic accuracy of ultrasound-guided fine needle aspiration biopsy (USFNA) for thyroid malignancy, and to explore the integration of these estimates with the probability of thyroid malignancy before USFNA. METHODS: A comprehensive search of multiple databases from each database's inception to August 2014 was performed. Eligible studies included those that evaluated patients with thyroid nodules who underwent USFNA and subsequent evaluation by histopathology or long-term follow-up. RESULTS: We identified 32 studies at moderate risk of bias evaluating the USFNA diagnostic characteristics for the diagnosis of thyroid malignancy. Results were imprecise and inconsistent across trials. The pooled likelihood ratio (LR) of thyroid malignancy for a benign USFNA result was 0.09 (95 % CI 0.06, 0.14; I (2) = 33 %), whereas the pooled LR for a malignant result was 197 (95 % CI, 68, 569; I (2) = 77 %). In the case of a suspicious for follicular neoplasm result, the pooled LR for malignancy was 0.6 (95 % CI, 0.4, 1.0; I (2) = 84 %) and 8.3 (95 % CI, 3.6, 19.2; I (2) = 89) for a result of suspicious for malignancy. CONCLUSION: The available evidence regarding the diagnostic accuracy of USFNA warrants only limited confidence due to risk of bias, imprecision, and inconsistency. However, some USFNA results (benign, malignant) are likely very helpful, by significantly changing the pre-test probability of thyroid cancer.

Outcomes of Parathyroidectomy in Patients with Primary Hyperparathyroidism: A Systematic Review and Meta-analysis.

BACKGROUND: Parathyroidectomy is a definitive treatment for primary hyperparathyroidism. Patients contemplating this intervention will benefit from knowledge regarding the expected outcomes and potential risks of the currently available surgical options. PURPOSE: To appraise and summarize the available evidence regarding benefits and harms of minimally invasive parathyroidectomy (MIP) and bilateral neck exploration (BNE). DATA SOURCES: A comprehensive search of multiple databases (MEDLINE, EMBASE, and Scopus) from each database's inception to September 2014 was performed. STUDY SELECTION: Eligible studies evaluated patients with primary hyperparathyroidism undergoing MIP or BNE. DATA EXTRACTION: Reviewers working independently and in duplicate extracted data and assessed the risk of bias. DATA SYNTHESIS: We identified 82 observational studies and 6 randomized trials at moderate risk of bias. Most of them reported outcomes after MIP (n = 71). Using random-effects models to pool results across studies, the cure rate was 98 % (95 % CI 97-98 %, I (2) = 10 %) with BNE and 97 % (95 % CI 96-98 %, I (2) = 86 %) with MIP. Hypocalcemia occurred in 14 % (95 % CI 10-17 % I (2) = 93 %) of the BNE cases and in 2.3 % (95 % CI 1.6-3.1 %, I (2) = 87 %) with MIP (P < 0.001). There was a statistically significant lower risk of laryngeal nerve injury with MIP (0.3 %) than with BNE (0.9 %), but similar risk of infection (0.5 vs. 0.5 %) and mortality (0.1 vs. 0.5 %). LIMITATIONS: The available evidence, mostly observational, is at moderate risk of bias, and limited by indirect comparisons and inconsistency for some outcomes (cure rate, hypocalcemia). CONCLUSION: MIP and BNE are both effective surgical techniques for the treatment of primary hyperparathyroidism. The safety profile of MIP appears superior to BNE (lower rate of hypocalcemia and recurrent laryngeal nerve injury).